Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo

De 2 första författarna delar förstaförfattarskapet.
Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross-presentation of antigen to CD8+ T cells. Mice with hapten-specific circulating antibodies, but naϊve for the T-cell antigen, were infused with haptenated antigen and CD8+ T-cell induction was measured. Mice with circulating hapten-specific antibodies showed significantly enhanced cross-presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross-presentation in mice with circulating antigen-specific antibodies was associated with improved antigen capture by APCs. Importantly, CD11c+ APCs were responsible for the enhanced and sustained cross-presentation, although CD11c− APCs had initially captured a significant amount of the injected antigen. Thus, in vivo formation of antigen-antibody immune complexes improves MHC class I cross-presentation, and CD8+ T-cell activation, demonstrating that humoral immunity can aid the initiation of systemic cellular immunity. These findings have important implications for the understanding of the action of therapeutic antibodies against tumor-associated antigens intensively used in the clinic nowadays.

Mangsbo, Sara MUppsala universitet,Institutionen för immunologi, genetik och patologi,Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands(Swepub:uu)saman132 (author)
Camps, Marcel G M (author)
van Maren, Wendy W C (author)
Verhaart, Ingrid E C (author)
Waisman, Ari (author)
Drijfhout, Jan Wouter (author)
Melief, Cornelis J M (author)
Verbeek, J Sjef (author)
Ossendorp, Ferry (author)
Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

By the author/editor: van Montfoort, N ...; Mangsbo, Sara M; Camps, Marcel G ...; van Maren, Wendy ...; Verhaart, Ingrid ...; Waisman, Ari; show more...; Drijfhout, Jan W ...; Melief, Cornelis ...; Verbeek, J Sjef; Ossendorp, Ferry; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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